Funded Projects

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (Collaborative U01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-21-020
Summary:

The objective of the HEALthy Brain and Child Development (HBCD) Prenatal Experiences and Longitudinal Development (PRELUDE) multi-site consortium is to characterize typical brain development from birth through childhood. All sites in this consortium will measure the influence of key biological and environmental factors on child social, cognitive, and emotional development. Researchers will assess how prenatal exposure to opioids and other substances, as well as other adverse environmental factors, affect brain development and other child health outcomes. The Arkansas Children’s Research Institute site is in a predominantly rural state with the second highest rate of opioid prescriptions in the U.S.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025
Summary:

The ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study – also called the ACT NOW Longitudinal Study – is a longitudinal cohort study to prospectively examine longitudinal outcomes from birth to 2 years of age among infants who were exposed to opioids in utero as compared to matched controls. The objectives of this study are to i) determine the impact of pre-birth opioid exposure on brain structure and connectivity over the first 2 years of life, ii) define medical, developmental, and behavioral outcomes over the first 2 years of life in infants exposed to opioids, and iii) Explore whether and how the home environment, maternal mental health, and parenting affect brain connectivity and neurodevelopment trajectories over the first 2 years of life. This research will use an innovative approach to engage a more diverse study population and thereby improve the generalizability of the research findings.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (Collaborative U01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-21-020
Summary:

The HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative model of developmental trajectories over the first 10 years of life. All sites in the HBCD-NC will carry out a common research protocol and will assemble and distribute a comprehensive research dataset to the scientific community. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. Most participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first 10 years of life. This study will take place at the University of Wisconsin, Madison, where researchers will have access to a diverse group of people, including women with criminal justice involvement.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (Collaborative U01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-21-020
Summary:

The HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative template of developmental trajectories over the first 10 years of life. All sites in the HBCD-NC will carry out a common research protocol and will assemble and distribute a comprehensive research dataset to the scientific community. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. Most participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first 10 years of life. The Northwestern University study site is in Chicago where rates of prenatal substance use are rising and consistent with the national trend. This site will recruit a diverse urban sample of mother-infant pairs reflecting the population of Chicago.

NOFO Number: PA-18-591
Summary:

Neonatal opioid withdrawal syndrome (NOWS) has emerged as a tragic by-product of the opioid epidemic. Newborns whose mothers used opioids while pregnant can experience symptoms of opioid withdrawal in the days following birth, such as tremors, irritability, seizures, sleep, digestive, and feeding problems. However, little is known about the effect of antenatal opioid exposure on longer-term infant development over time. To address this gap in understanding, the ACT NOW Longitudinal study is examining a crucial developmental period from birth to two years of life through a comprehensive battery of assessments, including MRI imaging, neurodevelopmental behavioral assessments, and family report measures. This longitudinal cohort study is projected to include a total of 375 infants, 250 who were exposed to opioids and 125 matched controls.

NOFO Number: N/A
Summary:

Due to the opioid misuse epidemic across the nation, more infants are being exposed to narcotics during fetal life and developing neonatal opioid withdrawal syndrome (NOWS) in the neonatal period. Critical gaps remain in our knowledge with respect to best practices for identifying and managing infants with NOWS and no large-scale studies have been published on treatments undertaken and later outcomes of infants with NOWS. To address these gaps in knowledge, the Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW) study will evaluate treatment options and improve clinical care of infants with NAS/NOWS. This collaborative effort will conduct two trials: 1) Eating, Sleeping, Consoling for Neonatal Withdrawal (ESC-NOW): a Function-Based Assessment and Management Approach (ESC Study); and 2) Pragmatic, Randomized, Blinded Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS) (Weaning Study).

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

Rates of neonatal abstinence syndrome have reached a staggering 6.5 per 1,000 births nationwide, creating an urgent need to identify how in-utero exposure to opioids and associated risk factors influence the developing brain. A multidisciplinary team will address these challenges in Oregon, a state particularly hard hit by the opioid epidemic. Through linking sites, the impact of the Phase I project is enhanced and will provide critical information to support a national-level effort for Phase II of the HEALthy Brain and Child Development Study. Aim 1 will develop, implement, and evaluate innovative recruitment and retention strategies for high-risk populations. Aim 2 will address anticipated challenges of the planned Phase II study by implementing and evaluating a multi-site, standardized research protocol including multimodal MRI of placenta, fetus, neonate, and 24-month-old brain; biospecimen collection; and assessment of substance use and other key domains. Aim 3 will evaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, and integration across sites.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-036
Summary:

Structural and functional neuroimaging measures are prone to errors induced by subject motion. Many comorbid features of opioid exposure are likely to increase children’s in-scanner motion. In total, this raises substantial concern that existing neuroimaging methods are not sufficiently motion-robust to be used in studies of children ages 3–5. Researchers will address these concerns with a feasibility study, comparing the existing methods developed for the Adolescent Brain Cognitive Development (ABCD) study with novel methods we will develop and optimize for young children. They will evaluate research methods in a sample of 100 children and test whether novel technologies improve the quality of the raw imaging data and reduce motion biases in the derived measures. Researchers will determine predictors of successful imaging to inform sampling strategies in future studies. The primary outcomes will be novel, validated structural and functional neuroimaging imaging methods for young children and feasibility data to inform the design of future studies addressing developmental questions, particularly those related to opioid exposure.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-036
Summary:

This project will support consortium hypothesis generation in Phase II in order to disentangle how complex environmental factors impact brain development and function — from fetal period through the first decade — to shape cognitive, social, and emotional development. The project will develop the strategies to recruit and retain a racially and ethnically diverse sample of pregnant women (and their fetuses), who are oversampled for adverse environmental risk factors and exposure to substances of abuse; develop the strategies for managing potential legal and ethical challenges to ensure that the mother–child dyads have access to legal, social, and psychological support services as needed; and determine the optimal study protocol for the planned, phase II study — balancing the need for high quality, longitudinal data collection with the need to minimize burden on the mother–child dyads.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

The Planning for the HEALthy Early Development Study will contribute to the design and recommended protocol for a future large-scale, multi-site research study to prospectively examine human brain, cognitive, behavioral, social, and emotional development of children beginning prenatally through ages 9–10 and to determine the impact of maternal pre- and postnatal substance use on short- and long-term development of children. The planning study will link investigators across 6 research sites who have complementary experience and expertise in the areas that are essential to designing the study. Planning activities will be accomplished using a coordinated set of 10 working groups. By the end of the planning phase, the 6 consortium sites will have produced and tested a recommended protocol for the future multi-site study and will have established feasibility of carrying out the study protocol at each of the 6 linked sites.

NOFO Title: HEAL Initiative: Antenatal Opioid Exposure Longitudinal Study Consortium (PL1 Clinical Trial Not Allowed)
NOFO Number: RFA-HD-19-025
Summary:

The incidence of Neonatal Opioid Withdrawal Syndrome (NOWS) in the United States has increased more than fivefold since 2004 to almost 7 per 1,000 hospital births. It is unknown how these effects are modulated by associated maternal, neonatal, and environmental factors and how the environment, maternal health, and parenting styles modify trajectories of brain connectivity and neurodevelopment. This study leverages the established infrastructure and longstanding collaborations of four clinical sites and the data coordinating center of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network to address current critical knowledge gaps in childhood brain structure and connectivity and on medical, developmental, and behavioral trajectories in early childhood. The study will analyze a well-characterized observational cohort using clinical and neuroimaging measures to improve understanding of the structural and functional sequelae resulting from prenatal opioid exposure and NOWS and their interactions with the maternal-infant dyad.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

Though prenatal exposure to opioids and other substances have adverse effects on neurodevelopment, advances in neuroimaging and developmentally sensitive phenotypic measurement now enable characterization of typical and atypical brain-behavior pathways on an unprecedented scale. The Brains Begin Before Birth (B4) Midwest Consortium, a partnership of neuroscience, substance use, perinatal mental health, and child welfare scientists at Washington University School of Medicine (WUSM) and neuroscience, bioethics, pediatric population health, maternal-fetal, and addiction scientists at Northwestern University (NU). This regional consortium will leverage the contrasting approaches of Illinois (punitive) and Missouri (non-punitive) to prenatal opioid use, providing a platform for examining the impact of jurisdictional variations on science and practice. The consortium provide a framework for addressing three major areas of challenge: (1) legal/ethical, (2) recruitment/retention, and (3) imaging/assessment methods.